6-azauridine triacetate has been previously described and utilized as a drug which is particularly useful in the treatment of psoriasis. 6-azauridine triacetate is prepared from 6-azauridine (6-azauracil riboside) by acetylation in accord with practices developed in the prior art. The 6-azauridine starting material to form the triacetate has been described in U.S. Pat. No. 3,468,759 as being formed from the 6-azauracil by a fermentation process. In turn, various methods have been described in the prior art for formulating the starting 6-azauracil. Perhaps the most effective process for forming 6-azauracil comprise the cyclization of glyoxylic acid semicarbazone. Thus, this semicarbazone is a valuable starting material in the synthesis of 6-azauracil, which in turn is utilized to form valuable drug products through additional reactions.
Applicant's U.S. Pat. Nos. 3,859,347 and 3,859,348 discloses methods for preparing glyoxylic acid semicarbazone. This semicarbazone may be cyclicized to 6-azauracil which, in turn, may be used to form 6-azauridine by fermentation techniques. 6-azauridine can be acetylated to form 6-azauridine triacetate. Prior to the herein invention, the preparation of nucleoside acetates has usually been carried out by treating the nucleoside with acetic anhydride and a catalyst such as pyridine, piperidine, zinc chloride, sulfuric acid, perchloric acid, sodium acetate, and at temperatures varying from room temperature or below, to the boiling point of water and sometimes even higher. Such prior methods suffer various shortcomings. The catalyst, for example, must be removed without causing decomposition of the desired product. This is often difficult and can effectively decrease the yield of the desired end product. Another drawback of the prior approaches is that the reaction is exothermic so that it is potentially extremely dangerous. Thus, they are impractical for large scale operations since there exists the possibility of damage to equipment and personnel, and loss of material. Additionally, in the prior processes, the isolation procedure causes decomposition, and purification of the product was necessary with attendant losses and added costs of labor and solvents, as well as requiring additional equipment. As the processes are scaled up, the problems, of course, become much more severe.
The herein method of acetylation which can be used for acetylating materials other than nucleosides as well, overcomes the disadvantages of the prior art. Major advantages of the method of this invention is that it provides essentially quantitative yield of the end product and this is extremely simple and can be run in a continuous or semi-continuous manner which reduces the cost of capital equipment, chemicals and labor. Furthermore, catalyst removal steps are eliminated.